Gene therapy expression system allowing an adequate expression in the muscles and in the heart of sgcg

Abstract

The present invention concerns an expression system for systemic administration comprising a sequence encoding gamma-sarcoglycan (SGCG) placed under the control of a promoter allowing an adequate expression of SGCG in the skeletal muscles and in the heart, and its use for the treatment of Limb-Girdle Muscular Dystrophy type C.

1 - 14 . (canceled) 
     
     
         15 . An expression system for systemic administration comprising a sequence encoding gamma-sarcoglycan (SGCG) placed under the control of a promoter allowing expression of SGCG in the skeletal muscles and in the heart, wherein the ratio between the SGCG expression in the skeletal muscles and the SGCG expression in the heart is superior or equal to 0.9. 
     
     
         16 . The expression system according to  claim 15 , wherein the system is configured to express SGCG in the skeletal muscles in a quantity superior or equal to 0.3 times a quantity expressed endogenous. 
     
     
         17 . The expression system according to  claim 15 , wherein the expression system is configured to express SGCG in the heart in a quantity inferior or equal to 8 times a quantity expressed endogenous. 
     
     
         18 . The expression system according to  claim 15 , wherein the promoter is a tMCK promoter. 
     
     
         19 . The expression system according to  claim 18 , wherein the tMCK promoter has a sequence as set forth in SEQ ID NO: 4. 
     
     
         20 . The expression system according to  claim 15 , wherein the SGCG protein has the sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         21 . The expression system according to  claim 15 , wherein the sequence encoding the SGCG protein has the sequence SEQ ID NO: 3. 
     
     
         22 . The expression system according to  claim 15 , wherein the expression system comprises SEQ ID NO: 5 or SEQ ID NO: 6. 
     
     
         23 . The expression system according to  claim 15 , wherein the expression system comprises a viral vector. 
     
     
         24 . The expression system according to  claim 23 , wherein the viral vector is an adeno-associated viral (AAV) vector. 
     
     
         25 . The expression system according to  claim 24 , wherein the AAV vector is of serotype 8 or 9. 
     
     
         26 . The expression system according to  claim 25 , wherein the expression system comprises an adeno-associated viral (AAV)2/8 or an AAV2/9 vector. 
     
     
         27 . A pharmaceutical composition comprising the expression system according to  claim 15 . 
     
     
         28 . The pharmaceutical composition according to  claim 27 , wherein the composition is a gene therapy composition. 
     
     
         29 . A method of treating a pathology caused by a SGCG deficiency, comprising administering the pharmaceutical composition according to  claim 27 . 
     
     
         30 . The method of  claim 29 , wherein the pathology caused by a SGCG deficiency is Limb-Girdle Muscular Dystrophy type C (LGMD2C or LGMD R5). 
     
     
         31 . The method of  claim 29 , wherein the pharmaceutical composition is administered systemically. 
     
     
         32 . The method of  claim 31 , wherein the pharmaceutical composition is administered by intravenous injection.